Primary Sclerosing CholangitisPhase 2BUTEONCT02239211
A Trial of BTT1023 in Patients With Primary Sclerosing Cholangitis
A Phase 2 study testing BTT1023 in people with Primary Sclerosing Cholangitis, run by University of Birmingham at 6 sites in United Kingdom.
Trial summary
This is a phase II study to determine the safety and preliminary efficacy of a human monoclonal antibody (BTT1023) which targets the vascular adhesion protein (VAP-1) and its use in the treatment of patients with primary sclerosing cholangitis (PSC). Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Primary Sclerosing Cholangitis
- What is being tested?
- BTT1023
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 6 sitesUnited Kingdom
- Study dates
- 8 Sep 2015to 23 Oct 2018
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Males and females 18 - 75 years of age who are willing and able to provide informed, written consent and comply with all trial requirements
- Clinical diagnosis of PSC as evident by chronic cholestasis of more than six months duration with either a consistent MRI showing sclerosing cholangitis or a liver biopsy consistent with PSC in the absence of a documented alternative aetiology for sclerosing cholangitis
- In those with concomitant Inflammatory Bowel Disease, clinical and colonoscopic evidence, (in line with the patient's standard of care; within 18 months) of stable disease, without findings of high grade dysplasia
- In those on treatment with UDCA, therapy must be stable for at least 3 months, and at a dose not greater than 20 mg/kg/day. In those not on treatment with UDCA at the time of screening, a minimum of 8 weeks since the last dose of UDCA should be recorded
- Serum ALP greater than 1.5 x ULN
- Stable serum ALP levels (levels must not change by more than 25% from Screening Visit 1 and Screening Visit 2)
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- Female subjects of childbearing potential must have a negative pregnancy test prior to starting trial treatment. For the purposes of this trial, a female subject of childbearing potential is a woman who has not had a hysterectomy, bilateral oophorectomy, or medically-documented ovarian failure. Women ≤ 50 years of age with amenorrhea of any duration will be considered to be of childbearing potential
- All sexually active women of childbearing potential must agree to use two forms of highly effective method of contraception from the Screening Visit throughout the trial period and for 99 days following the last dose of trial drug. If using hormonal agents the same method must have been used for at least 1 month before trial dosing and subjects must use a barrier method as the other form of contraception. Lactating women must agree to discontinue breast feeding before trial investigational medicinal product administration
- Men, if not vasectomised, must agree to use barrier contraception (condom plus spermicide) during heterosexual intercourse from screening through to trial completion and for 99 days from the last dose of trial investigational medicinal product
- Patients must weigh ≥ 40 kg
Who cannot join
- Presence of documented secondary sclerosing cholangitis on prior clinical investigations
- Presence of alternative causes of liver disease, that are considered by the Investigator to be the predominant active liver injury at the time of screening, including viral hepatitis, alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis. Patients with possible overlap syndrome with autoimmune hepatitis are excluded if the Investigator considers autoimmune hepatitis as the predominant liver injury
- AST and ALT >10 x ULN or bilirubin >3 x ULN or INR >1.3 in the absence of anti-coagulants
- Serum creatinine >130μmol/L or platelet count <50 x 109/L
- Any evidence of hepatic decompensation past or present, including ascites, episodes of hepatic encephalopathy or variceal bleeding
- Recent cholangitis within last 90 days or ongoing need for prophylactic antibiotics
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- Pregnancy or breast feeding
- Harmful alcohol consumption as evaluated by the Investigator
- Flare in colitis activity within last 90 days requiring intensification of therapy beyond baseline maintenance treatment; use of oral prednisolone >10 mg/day, biologics (i.e. monoclonal antibodies) and or hospitalisation for colitis within 90 days. Prior use of biologics is not a contraindication to screening
- Diagnosed cholangiocarcinoma or high clinical suspicion of cholangiocarcinoma either clinically or by imaging
- Concurrent malignancies or invasive cancers diagnosed within past 3 years except for adequately treated basal cell and squamous cell carcinoma of the skin and in situ carcinoma of the uterine cervix
- Presence of a percutaneous drain or bile duct stent
- Major surgical procedure within 30 days of screening
- Prior organ transplantation
- Known hypersensitivity to the investigational product or any of its formulation excipients
- Unavailable for follow-up assessment or concern for subject's compliance
- Participation in an investigational trial of a drug or device within 60 days of screening or 5 half lives of the last dose of investigational drug, where the trial drug half-life is greater than 12 days
- Any other condition that in the opinion of the Investigator renders the subject a poor risk for inclusion into the trial
- Positive screening test for tuberculosis (TB) (including T-SPOT.TB TB test), unless respiratory review confirms false positive test results
- Receipt of live vaccination within 6 weeks prior to Screening Visit 2
- Known HIV positive status
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United Kingdom6 sites
University Hospitals Birmingham NHS Foundation Trust
Birmingham, West Midlands, B15 2TH
Addenbrooke's Hospital
Cambridge
Royal Free Hospital
London
Royal Victoria Infirmary
Newcastle
Queens Medical Centre
Nottingham, Nottinghamshire, NG7 2UH
John Radcliffe Hospital
Oxford
About this study
Official title: A Single Arm, Two-stage, Multi-centre, Phase II Clinical Trial Investigating the Safety and Activity of the Use of BTT1023 Targeting Vascular Adhesion Protein (VAP-1), in the Treatment of Patients With Primary Sclerosing Cholangitis (PSC).
This is a phase II study to determine the safety and preliminary efficacy of a human monoclonal antibody (BTT1023) which targets the vascular adhesion protein (VAP-1) and its use in the treatment of patients with primary sclerosing cholangitis (PSC).
Read the detailed description
Primary sclerosing cholangitis is a progressive immune mediated biliary disease characterised by bile duct inflammation and fibrosis, and accompanying hepatic fibrosis. For patients with elevated alkaline phosphatase (ALP) in particular, progressive disease is predicted, that currently results in a need for liver transplantation in the majority. No current medical therapy has as yet been shown to be effective in altering the natural history of disease. For this reason patients with PSC with elevated ALP values will be recruited to this study, to evaluate the impact of Vap-1 blockade by BTT1023, in an early phase study focused on biochemical efficacy and safety.
This is an early phase study of BTT1023 in immune mediated liver disease, with the rationale to identify biochemical efficacy of effect (reduction in ALP) and safety, in an orphan disease indication for PSC that presently lacks any other medical therapy. The study design therefore focuses on identifying early biochemical efficacy signals to justify larger scale, randomised controlled studies over longer duration.
- Conditions
- Primary Sclerosing Cholangitis
- Being tested
- BTT1023
- Keywords
- BUTEO, Primary sclerosing cholangitis, PSC, VAP-1, BTT1023, Human monoclonal antibody
- Medical subject headings
- Cholangitis, Sclerosing
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BTT1023Drug
IV (in the vein) Investigational Medicinal Product (IMP)
| Study group | Role | What they receive |
|---|---|---|
| BTT1023 | Experimental | BTT1023 8mg/kg IV infusion, total of 7 infusions over 11 weeks. Duration 1-2 hours per infusion. Receives: Drug: BTT1023 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response at Visit 10 (Day 99): a reduction in serum ALP by 25% or more from baseline to Visit 10 (Day 99)
Measured: 99 days
Secondary outcomes (19)
Treatment Compliance (including patient withdrawal)
These will be measured to evaluate the tolerability of BTT1203 in patients with PSC
Measured: 120 days
Serious Adverse Event (SAE) frequency
These will be measured to evaluate the safety, effective dose, and tolerability of BTT1203 in patients with PSC
Measured: 120 days
Adverse Event (AE) frequency
These will be measured to evaluate the safety, effective dose, and tolerability of BTT1203 in patients with PSC
Measured: 120 days
Calculation of any change (improvement or worsening) from baseline to Day 99 in the quality of life questionnaire EQ-5D
Using validated EQ-5D scoring system
Measured: 99 days
Calculation of any change (improvement or worsening) from baseline to Day 99 in the quality of life questionnaire Fatigue Severity Scale
The scoring is done by calculating the average response to the questions (adding up all the answers and dividing by nine).
Measured: 99 days
Calculation of any change (improvement or worsening) from baseline to Day 99 in the quality of life questionnaire Pruritus Visual Analogue Score
VAS measured as per guidelines
Measured: 99 days
Calculation of any change (improvement or worsening) from baseline to Day 99 in Inflammatory Bowel Disease Diaries (if applicable)
Measured: 99 days
Calculation of any change (improvement or worsening) from baseline to Day 99 in enhanced liver fibrosis test
Measured: 99 days
Calculation of any change (improvement or worsening) from baseline to Day 99 in Fibroscan measures
Measured: 99 days
Calculation of any change (improvement or worsening) from baseline to Day 99 in Aspartate Transaminase (AST)
Measured: 99 days
Calculation of any change (improvement or worsening) from baseline to Day 99 in Alanine Transaminase (ALT)
Measured: 99 days
Calculation of any change (improvement or worsening) from baseline to Day 99 in Alkaline Phosphatase (ALP)
Measured: 99 days
Calculation of any change (improvement or worsening) from baseline to Day 99 in Gamma Glutamyl Transferase (GGT)
Measured: 99 days
Calculation of any change (improvement or worsening) from baseline to Day 99 in Bilirubin
Measured: 99 days
Calculation of any change (improvement or worsening) from baseline to Day 99 in Albumin
Measured: 99 days
Calculation of any change (improvement or worsening) from baseline to Day 99 in International Normalised Ratio (INR)
Measured: 99 days
Calculation of any change (improvement or worsening) from baseline to Day 99 in Mayo PSC Risk Score
PSC Risk score calculated as per The Revised Natural History Model for Primary Sclerosing Cholangitis
Measured: 99 days
Calculation of any change (improvement or worsening) from baseline to Day 99 in Model for End Stage Liver Disease (MELD) Score
MELD calculated as per pre 2016 guidelines
Measured: 99 days
Evaluate changes (improvement or worsening) in sVAP-1/SSAO as a biomarker of liver disease activity across the trial period
Measured: 120 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Sep 2014 (estimated)
- Study start8 Sep 2015
- Primary completion23 Oct 2018
- Study completion23 Oct 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Primary Sclerosing CholangitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Birmingham
- Sponsor type
- University, hospital or other
- Collaborators
- Biotie Therapies Corp., University Hospital Birmingham, National Institute for Health Research, United Kingdom
- Responsible party
- Sponsor
- Investigators
- Philip Newsome, MD, Principal investigator, University of Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02239211
- Sponsor's protocol ID
- RG_13-027
- Other IDs
- 2014-002393-37, 2014
- Acronym
- BUTEO
- Status last verified
- Apr 2019
- First submitted
- 4 Sep 2014
- Last updated
- 3 May 2019
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Arndtz K, Corrigan M, Rowe A, Kirkham A, Barton D, Fox RP, Llewellyn L, Athwal A, Wilkhu M, Chen YY, Weston C, Desai A, Adams DH, Hirschfield GM; BUTEO trial team. Investigating the safety and activity of the use of BTT1023 (Timolumab), in the treatment of patients with primary sclerosing cholangitis (BUTEO): A single-arm, two-stage, open-label, multi-centre, phase II clinical trial protocol. BMJ Open. 2017 Jul 3;7(6):e015081. doi: 10.1136/bmjopen-2016-015081.
PubMed 28674140
Study at a glance
From the registry record, last updated by the sponsor on 3 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single Arm, Two-stage, Multi-centre, Phase II Clinical Trial Investigating the Safety and Activity of the Use of BTT1023 Targeting Vascular Adhesion Protein (VAP-1), in the Treatment of Patients With Primary Sclerosing Cholangitis (PSC).
- ClinicalTrials.gov ID
- NCT02239211
- Acronym / sponsor ID
- BUTEO / RG_13-027
- Conditions
- Primary Sclerosing Cholangitis
- Keywords
- BUTEO, Primary sclerosing cholangitis, PSC, VAP-1, BTT1023, Human monoclonal antibody
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- University of BirminghamUniversity, hospital or other
- Collaborators
- Biotie Therapies Corp., University Hospital Birmingham, National Institute for Health Research, United Kingdom
- Study start
- 8 Sep 2015 (actual)
- Primary completion
- 23 Oct 2018 (actual)
- Study completion
- 23 Oct 2018 (actual)
- First posted
- 12 Sep 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a phase II study to determine the safety and preliminary efficacy of a human monoclonal antibody (BTT1023) which targets the vascular adhesion protein (VAP-1) and its use in the treatment of patients with primary sclerosing cholangitis (PSC).
Detailed description
Primary sclerosing cholangitis is a progressive immune mediated biliary disease characterised by bile duct inflammation and fibrosis, and accompanying hepatic fibrosis. For patients with elevated alkaline phosphatase (ALP) in particular, progressive disease is predicted, that currently results in a need for liver transplantation in the majority. No current medical therapy has as yet been shown to be effective in altering the natural history of disease. For this reason patients with PSC with elevated ALP values will be recruited to this study, to evaluate the impact of Vap-1 blockade by BTT1023, in an early phase study focused on biochemical efficacy and safety.
This is an early phase study of BTT1023 in immune mediated liver disease, with the rationale to identify biochemical efficacy of effect (reduction in ALP) and safety, in an orphan disease indication for PSC that presently lacks any other medical therapy. The study design therefore focuses on identifying early biochemical efficacy signals to justify larger scale, randomised controlled studies over longer duration.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| BTT1023 | Experimental | Drug: BTT1023BTT1023 8mg/kg IV infusion, total of 7 infusions over 11 weeks. Duration 1-2 hours per infusion. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Males and females 18 - 75 years of age who are willing and able to provide informed, written consent and comply with all trial requirements
- Clinical diagnosis of PSC as evident by chronic cholestasis of more than six months duration with either a consistent MRI showing sclerosing cholangitis or a liver biopsy consistent with PSC in the absence of a documented alternative aetiology for sclerosing cholangitis
- In those with concomitant Inflammatory Bowel Disease, clinical and colonoscopic evidence, (in line with the patient's standard of care; within 18 months) of stable disease, without findings of high grade dysplasia
- In those on treatment with UDCA, therapy must be stable for at least 3 months, and at a dose not greater than 20 mg/kg/day. In those not on treatment with UDCA at the time of screening, a minimum of 8 weeks since the last dose of UDCA should be recorded
- Serum ALP greater than 1.5 x ULN
Key exclusion criteria (21 listed)
- Presence of documented secondary sclerosing cholangitis on prior clinical investigations
- Presence of alternative causes of liver disease, that are considered by the Investigator to be the predominant active liver injury at the time of screening, including viral hepatitis, alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis. Patients with possible overlap syndrome with autoimmune hepatitis are excluded if the Investigator considers autoimmune hepatitis as the predominant liver injury
- AST and ALT >10 x ULN or bilirubin >3 x ULN or INR >1.3 in the absence of anti-coagulants
- Serum creatinine >130μmol/L or platelet count <50 x 109/L
- Any evidence of hepatic decompensation past or present, including ascites, episodes of hepatic encephalopathy or variceal bleeding
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BTT1023IV (in the vein) Investigational Medicinal Product (IMP) | Drug | BTT1023 |
Primary outcome
Response at Visit 10 (Day 99): a reduction in serum ALP by 25% or more from baseline to Visit 10 (Day 99)
Time frame: 99 days
19 secondary outcomes
Treatment Compliance (including patient withdrawal)
Time frame: 120 days
Serious Adverse Event (SAE) frequency
Time frame: 120 days
Adverse Event (AE) frequency
Time frame: 120 days
Calculation of any change (improvement or worsening) from baseline to Day 99 in the quality of life questionnaire EQ-5D
Time frame: 99 days
Calculation of any change (improvement or worsening) from baseline to Day 99 in the quality of life questionnaire Fatigue Severity Scale
Time frame: 99 days
Calculation of any change (improvement or worsening) from baseline to Day 99 in the quality of life questionnaire Pruritus Visual Analogue Score
Time frame: 99 days
Calculation of any change (improvement or worsening) from baseline to Day 99 in Inflammatory Bowel Disease Diaries (if applicable)
Time frame: 99 days
Calculation of any change (improvement or worsening) from baseline to Day 99 in enhanced liver fibrosis test
Time frame: 99 days
Calculation of any change (improvement or worsening) from baseline to Day 99 in Fibroscan measures
Time frame: 99 days
Calculation of any change (improvement or worsening) from baseline to Day 99 in Aspartate Transaminase (AST)
Time frame: 99 days
Calculation of any change (improvement or worsening) from baseline to Day 99 in Alanine Transaminase (ALT)
Time frame: 99 days
Calculation of any change (improvement or worsening) from baseline to Day 99 in Alkaline Phosphatase (ALP)
Time frame: 99 days
Calculation of any change (improvement or worsening) from baseline to Day 99 in Gamma Glutamyl Transferase (GGT)
Time frame: 99 days
Calculation of any change (improvement or worsening) from baseline to Day 99 in Bilirubin
Time frame: 99 days
Calculation of any change (improvement or worsening) from baseline to Day 99 in Albumin
Time frame: 99 days
Calculation of any change (improvement or worsening) from baseline to Day 99 in International Normalised Ratio (INR)
Time frame: 99 days
Calculation of any change (improvement or worsening) from baseline to Day 99 in Mayo PSC Risk Score
Time frame: 99 days
Calculation of any change (improvement or worsening) from baseline to Day 99 in Model for End Stage Liver Disease (MELD) Score
Time frame: 99 days
Evaluate changes (improvement or worsening) in sVAP-1/SSAO as a biomarker of liver disease activity across the trial period
Time frame: 120 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 May 2019.
- Derived from this study: PubMed 28674140Arndtz K, Corrigan M, Rowe A, Kirkham A, Barton D, Fox RP, Llewellyn L, Athwal A, Wilkhu M, Chen YY, Weston C, Desai A, Adams DH, Hirschfield GM; BUTEO trial team. Investigating the safety and activity of the use of BTT1023 (Timolumab), in the treatment of patients with primary sclerosing cholangitis (BUTEO): A single-arm, two-stage, open-label, multi-centre, phase II clinical trial protocol. BMJ Open. 2017 Jul 3;7(6):e015081. doi: 10.1136/bmjopen-2016-015081.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Philip Newsome, MD principal investigator
University of Birmingham
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing BTT1023 in people with Primary Sclerosing Cholangitis, run by University of Birmingham at 6 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 May 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Response at Visit 10 (Day 99): a reduction in serum ALP by 25% or more from baseline to Visit 10 (Day 99) (time frame: 99 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02239211, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 May 2019.